BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LOSS OF SULFITE OXIDASE ACTIVITY AND OUTER MEMBRANE DAMAGE IN RAT HEPATIC MITOCHONDRIA DURING Ccl4 POISONING

The activity of sulfite oxidase increased in intact rat hepatic mltochondria and decreased in solubilized mitochondria during poisoning by cc1 iI' During acute damage the sulfite oxidase activity of the post-mitocho drial supernate increased, while the total activity in the hepatocyte declined. Thus, the outer membrane loses its selective permeability to macromolecules coincident with the decline of oxidative phosphorylation. In recovery, normal levels of activity in intact mitochondria and in the hepatocyte were restored, but a large proportion of the total activity remained in the cytoplasm. The data suggest that outer membrane repair and replacement of sulfite oxidase are involved in the restoration of mitochondrial structure and function. One characteristic of acute carbon tetrachloride poisoning is damage to hepatic mitochondria (1). The damage is indicated by a loss of coupled respiration, a decrease of protein and nucleic acid synthesis (Z), and an alteration of morphological appearance (3). Hepatic levels of ATP decline in a manner parallel to the loss of coupled respiration (4). I f the exposure to Ccl4 is sub-lethal, a restoration of the damage occurs (2). Because mitochondrial damage occurs after other CCl4-induced cytoplasmic disturbances are well advanced, the conditions which are responsible for the damage are uncertain as yet. Further, the complexity of oxidative phosphorylation makes it difficult to discern the mitochondrial components involved in the dysfunction. A less complex aspect of mitochondrial integrity is the condition of the outer membrane. This study reports that the outer membrane of the hepatic mitochondrion is damaged during Ccl4 poisoning. This damage is revealed by the release of an intramembranal enzyme, sulfite oxidase (EC 1.8.3.1) from the organelle, and a